A bidirectional Hopf bifurcation analysis of Parkinson's oscillation in a simplified basal ganglia model.

In this paper, we study the parkinson oscillation mechanism in a computational model by bifurcation analysis and numerical simulation. Oscillatory activities can be induced by abnormal coupling weights and delays. The bidirectional Hopf bifurcation phenomena are found in simulations, which can uniformly explain the oscillation mechanism in this model. The Hopf1 represents the transition between the low firing rate stable state (SS) and oscillation state (OS), the Hopf2 represents the transition between the high firing rate stable state (HSS) and the OS, the mechanisms of them are different. The Hopf1 and Hopf2 bifurcations both show that when the state transfers from the stable region to the oscillation region, oscillatory activities originate from the beta frequency band or the gamma frequency band. We find that the changing trends of the frequency (DF) and oscillation amplitude (OSAM) are contrary in many cases. The effect of the delay in inhibitory pathways is greater than that of in excitatory pathways, and appropriate delays improve the discharge activation level (DAL) of the system. In all, we infer that oscillations can be induced by the follow factors: 1. Improvement of the DAL of the globus pallidus externa (GPe); 2. Reduce the DAL of the GPe from the HSS or the discharge saturation state; 3. The GPe can also resonate with the subthalamic nucleus (STN).

Mathematical derivation and mechanism analysis of beta oscillations in a cortex-pallidum model.

In this paper, we develop a new cortex-pallidum model to study the origin mechanism of Parkinson's oscillations in the cortex. In contrast to many previous models, the globus pallidus internal (GPi) and externa (GPe) both exert direct inhibitory feedback to the cortex. Using Hopf bifurcation analysis, two new critical conditions for oscillations, which can include the self-feedback projection of GPe, are obtained. In this paper, we find that the average discharge rate (ADR) is an important marker of oscillations, which can divide Hopf bifurcations into two types that can uniformly be used to explain the oscillation mechanism. Interestingly, the ADR of the cortex first increases and then decreases with increasing coupling weights that are projected to the GPe. Regarding the Hopf bifurcation critical conditions, the quantitative relationship between the inhibitory projection and excitatory projection to the GPe is monotonically increasing; in contrast, the relationship between different coupling weights in the cortex is monotonically decreasing. In general, the oscillation amplitude is the lowest near the bifurcation points and reaches the maximum value with the evolution of oscillations. The GPe is an effective target for deep brain stimulation to alleviate oscillations in the cortex.

The mechanism of Parkinson oscillation in the cortex: Possible evidence in a feedback model projecting from the globus pallidus to the cortex.

The origin, location and cause of Parkinson's oscillation are not clear at present. In this paper, we establish a new cortex-basal ganglia model to study the origin mechanism of Parkinson beta oscillation. Unlike many previous models, this model includes two direct inhibitory projections from the globus pallidus external (GPe) segment to the cortex. We first obtain the critical calculation formula of Parkinson's oscillation by using the method of Quasilinear analysis. Different from previous studies, the formula obtained in this paper can include the self-feedback connection of GPe. Then, we use the bifurcation analysis method to systematically explain the influence of some key parameters on the oscillation. We find that the bifurcation principle of different cortical nuclei is different. In general, the increase of the discharge capacity of the nuclei will cause oscillation. In some special cases, the sharp reduction of the discharge rate of the nuclei will also cause oscillation. The direction of bifurcation simulation is consistent with the critical condition curve. Finally, we discuss the characteristics of oscillation amplitude. At the beginning of the oscillation, the amplitude is relatively small; with the evolution of oscillation, the amplitude will gradually strengthen. This is consistent with the experimental phenomenon. In most cases, the amplitude of cortical inhibitory nuclei (CIN) is greater than that of cortical excitatory nuclei (CEX), and the two direct inhibitory projections feedback from GPe can significantly reduce the amplitude gap between them. We calculate the main frequency of the oscillation generated in this model, which basically falls between 13 and 30 Hz, belonging to the typical beta frequency band oscillation. Some new results obtained in this paper can help to better understand the origin mechanism of Parkinson's disease and have guiding significance for the development of experiments.

Quasilinearization method for an impulsive integro-differential system with delay.

In this paper, we obtain solution sequences converging uniformly and quadratically to extremal solutions of an impulsive integro-differential system with delay. The main tools are the method of quasilinearization and the monotone iterative. The results obtained are more general and applicable than previous studies, especially the quadratic convergence of the solution for a class of integro-differential equations, which have been involved little by now.

The inhibition mechanism of epilepsy disease in a computational model.

BACKGROUND: The mechanism of prevention and treatment of epilepsy is a hot issue in theoretical research. OBJECTIVE: In this paper, we studied the control mechanism of the generalized spike-and-wave discharges (GSWD) by different types of external electrical stimulation acting on the subthalamic nucleus (STN) in a computational model. METHODS: Firstly, we analyzed the pathological mechanism of seizures, which were induced by different parameters in the thalamocortical (TC) circuit. Then, a voltage V was exerted in the STN. At last, we used the sine wave and square wave current stimulation in the STN. RESULTS: We found that seizures can be inhibited by tuning stimulus intensity into suitable range, and the direction of adjustment depended on the size of the parameter. We observed that the seizure can also be inhibited by tuning different parameters in current. CONCLUSIONS: Different inhibition mechanisms can be explained in this model, which may provide theoretical evidences for selecting the optimal treatment scheme in the clinical.

The adjustment mechanism of the spike and wave discharges in thalamic neurons: a simulation analysis.

Different from many previous theoretical studies, this paper explores the regulatory mechanism of the spike and wave discharges (SWDs) in the reticular thalamic nucleus (TRN) by a dynamic computational model. We observe that the SWDs appears in the TRN by changing the coupling weights and delays in the thalamocortical circuit. The abundant poly-spikes wave discharges is also induced when the delay increases to large enough. These discharges can be inhibited by tuning the inhibitory output from the basal ganglia to the thalamus. The mechanisms of these waves can be explained in this model together with simulation results, which are different from the mechanisms in the cortex. The TRN is an important target in treating epilepsy, and the results may be a theoretical evidence for experimental study in the future.

Existence of solutions of an impulsive integro-differential equation with a general boundary value condition.

In this paper, we discuss the existence of solutions for a first-order nonlinear impulsive integro-differential equation with a general boundary value condition. New comparison principles are developed, and existence results for extremal solutions are obtained using the established principles and the monotone iterative technique. The results are more general than those of the periodic boundary problems, which may be widely applied in this field.

The therapeutic mechanism of epilepsy seizures in different target areas: Research on a theoretical model.

BACKGROUND: The selection of optimal target areas in the surgical treatment of epilepsy is always a difficult problem in medicine. OBJECTIVE: We employed a theoretical calculation model to explore the control mechanism of seizures by an external voltage stimulus acting in different nerve nuclei. METHODS: Theoretical analysis and numerical simulation were combined. RESULTS: The globus pallidus, excitatory pyramidal neurons, striatal D1 neurons, thalamic reticular nucleus and specific relay nuclei were selected, we analyzed that the electrical stimulation has different effects in these target areas. CONCLUSIONS: The data selected were reasonable in study, the results may give a theoretical support for similar studies in clinical.

The theoretical mechanism of Parkinson's oscillation frequency bands: a computational model study.

Excessive synchronous oscillation activities appear in the brain is a key pathological feature of Parkinson's disease, the mechanism of which is still unclear. Although some previous studies indicated that ß oscillation (13-30 Hz) may directly originate in the network composed of the subthalamic nucleus (STN) and external globus pallidus (GPe) neurons, specific onset mechanisms of which are unclear, especially theoretical evidences in numerical simulation are still little. In this paper, we employ a STN-GPe mean-field model to explore the onset mechanism of Parkinson's oscillation. In addition to ß oscillation, we find that some other common oscillation frequency bands can appear in this network, such as the α oscillation band (8-12 Hz), the θ oscillation band (4-7 Hz) and δ oscillation band (1-3 Hz). In addition to the coupling weight between the STN and GPe, the delay is also a critical factor to affect oscillatory activities, which can not be neglected compared to other parameters. Through simulation and analysis, we propose two possible theories may induce the system to transfer from the stable state to the oscillatory state in this model: (1). The oscillation activity can be induced when the firing activation level of the population increases to large enough; (2). In some special cases, the population may stay in the high firing rate stable state and the mean discharge rate of which is too large to induce oscillations, then oscillation activities may be induced as the MD decreases to moderate value. In most situations, the change trends of the MD and oscillation dominant frequency are contrary, which may be an important physiological phenomenon shown in this model. The delays and firing rates were obtained by simulating, which may be verified in the experiment in the future.